Transition-state structures, Grignard reagent

The high diastereoselectivity which is found in the nucleophilic addition of Grignard reagents to chiral 2-0x0 acetals can be explained by a chelation-controlled mechanism. Thus, coordination of the magnesium metal with the carbonyl oxygen and the acetal moiety leads to a rigid structure 3A in the transition state with preferred attack of the nucleophile occurring from the S/-side. 

The diastereoselectivity of the reaction may be rationalized by assuming a chelation model, which has been developed in the addition of Grignard reagents to enantiomerically pure a-keto acetals7,8. Cerium metal is fixed by chelation between the N-atom, the methoxy O-atom and one of the acetal O-atoms leading to a rigid structure in the transition state of the reaction (see below). Hence, nucleophilic attack from the Si-face of the C-N double bond is favored4. 

For ketones and aldehydes in which adjacent substituents permit chelation with the metal ion in the transition state, the stereochemistry can often be interpreted in terms of the steric requirements of the chelated transition state. In the case of a-alkoxyketones, for example, an assumption that both the alkoxy and carbonyl oxygens will be coordinated with the metal ion and that addition will occur from the less hindered side of this structure correctly predicts the stereochemistry of addition. The predicted product dominates by as much as 100 1 for several Grignard reagents." Further supporting the importance of chelation is the correlation between rate and stereoselectivity. Groups which facilitate chelation cause an increase in both rate and stereoselectivity.99 100... 

Another notable difference between the Zr-catalyzed ethylmagnesations of allylic ethers and alcohols is the effect of solvent Lewis basicity on reaction selectivity. Thus, as iUustrated in Scheme 3.79, whereas reactions with allylic ethers are entirely insensitive to variations in solvent structure, those of allylic alcohols are strongly influenced. These observations led Hoveyda and coworkers to conclude that for allylic alcohols (allyhc alkoxides after rapid deprotonation by the Grignard reagent) there is chelation between the Lewis basic heteroatom and a metal center (Zr or Mg) this association, which gives rise to transition state organization and high diastereocon-trol, is altered in the presence of Lewis basic THF, with diminution in selectivity. 

Organic bromides fall between iodides and chlorides, the rate-controlling step containing contributions from mass transfer and chemical reaction. Hammett p constants for bromobenzene support any of the last three transition states. In the last of the four papers " rate-structure profiles for the formation of Grignard reagents are shown to correlate, with coefficients between 0.73 and 0.99, with other processes involving the electrochemical and chemical reduction of alkyl halides. 

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